在内分泌治疗 (ET) 加 CDK4/6 抑制剂导致疾病进展后，雌激素受体阳性 (ER) 转移性乳腺癌 (MBC) 的后续治疗方案尚无标准化序列。 CDK4/6i 重试作为一种治疗策略在现代临床实践中很常见；然而，调查这一策略的现有前瞻性数据并没有得出结论性的结果。为了在现实世界中构建这些数据，我们进行了一项回顾性分析，评估了 CDK4/6is 对 195 名患者的疗效，这些患者之前在我们机构的先前治疗线中接触过 CDK4/6i。在因毒性而停止 CDK4/6i 的患者中，在使用不同的 CDK4/6i 后立即重新试验 CDK4/6i 或使用相同的初始 CDK4/6i 进行进一步治疗既安全又有效，中位时间达到治疗失败 (TTF) 为 10.1 个月 (95% CI, 4.8-16.9)。对于先前接受过 CDK4/6i 治疗后疾病进展的患者，我们证明了使用相同 CDK4/6i 重新挑战的患者（4.3 个月，95% CI 3.2-5.5）和使用不同 CDK4/6i（4.7 个月，95%）的中位 TTF 相当。 CI 3.7-6.0）与最近的 PACE、PALMIRA 和 MAINTAIN 试验相比。探索性基因组分析表明，已知赋予 CDK4/6i 耐药性的突变的存在，例如 TP53 突变、CDK4 扩增和 RB1 或 FAT1 功能丧失突变，可能是预测 CDK4/6i 重试失败的分子生物标志物。© 2024。作者（s）。

After disease progression on endocrine therapy (ET) plus a CDK4/6 inhibitor, there is no standardized sequence for subsequent treatment lines for estrogen receptor positive (ER+) metastatic breast cancer (MBC). CDK4/6i retrial as a treatment strategy is commonplace in modern clinical practice; however, the available prospective data investigating this strategy have had inconclusive results. To frame this data in a real-world context, we performed a retrospective analysis assessing the efficacy of CDK4/6is in 195 patients who had previous exposure to CDK4/6i in a prior treatment line at our institution. Among patients who had stopped a CDK4/6i due to toxicity, CDK4/6i retrial either immediately after with a different CDK4/6i or in a further treatment line with the same initial CDK4/6i was both safe and effective, with a median time to treatment failure (TTF) of 10.1 months (95%CI, 4.8-16.9). For patients whose disease progressed on a prior CDK4/6i, we demonstrated comparable median TTFs for patients rechallenged with the same CDK4/6i (4.3 months, 95%CI 3.2-5.5) and with a different CDK4/6i (4.7 months, 95%CI 3.7-6.0) when compared to the recent PACE, PALMIRA, and MAINTAIN trials. Exploratory genomic analysis suggested that the presence of mutations known to confer CDK4/6i resistance, such as TP53 mutations, CDK4 amplifications, and RB1 or FAT1 loss of function mutations may be molecular biomarkers predictive of CDK4/6i retrial failure.© 2024. The Author(s).